Abstract
Intertumor heterogeneity has been proposed as a potential mechanism to account for variability in cognitive performance in women diagnosed with breast cancer. The purpose of this study was to explore associations between variation in pathologic tumor features (PTFs) and variability in preadjuvant therapy cognitive performance in postmenopausal women newly diagnosed with early‐stage breast cancer. Participants (N = 329) completed a comprehensive battery of neuropsychological tests to evaluate cognitive performance after primary surgery but prior to initiation of adjuvant anastrozole±chemotherapy. PTF data were abstracted from medical records. Robust multiple linear regression models were fit to estimate associations between individual PTFs and the cognitive function composite domain scores. All models controlled for age, estimated intelligence, and levels of depressive symptoms, anxiety, fatigue, and pain. Diagnosis of a HER2‐positive tumor contributed to poorer verbal (b = −0.287, P = 0.018), visual (b = −0.270, P = 0.001), and visual working (b = −0.490, P < 0.001) memory performance compared to diagnosis of a HER2‐negative tumor. Similarly, as HER2 immunohistochemistry classification score increased, verbal (b = −0.072, P = 0.093), visual (b = −0.081, P = 0.003), and visual working (b = −0.170, P < 0.001) memory performance score decreased. Associations with performance were also noted between location, focality/centricity, hormone receptor expression, cellular proliferation (i.e., Ki67), and Oncotype DX ® Breast Cancer Assay Recurrence Score®.) Our results suggest that certain PTFs related to more aggressive tumor phenotypes or inferior breast cancer prognosis may be implicated in poorer preadjuvant therapy cognitive performance. Follow‐up studies that include a cognitive assessment before primary surgery should be conducted to further delineate the role of intertumor heterogeneity on cognitive performance.
Highlights
Current studies suggest that approximately 20–40% of women newly diagnosed with breast cancer experience lower than expected cognitive performance prior to receiving adjuvant breast cancer therapy [1,2,3,4]
Of the 369 women diagnosed with early-stage breast cancer enrolled in the parent study, 329 participants had pathologic tumor feature (PTF) data collected and complete confounder/covariate information and cognitive function scores available for one or more cognitive function composite domains (Table 1)
A comparison of characteristics of participants included (n = 329) to those not included because PTF or pretreatment cognitive function data were not available or covariate/confounder information was incomplete (n = 40) revealed that participants not included in the analysis had poorer (P = 0.011) median attention performance Z-scores (25% = −1.11, 50% = −0.43, 75% = 0.11) than participants included in the analysis (25% = −0.66, 50% = −0.12, 75% = 0.51)
Summary
Current studies suggest that approximately 20–40% of women newly diagnosed with breast cancer experience lower than expected cognitive performance prior to receiving adjuvant breast cancer therapy [1,2,3,4]. Findings that only a subgroup of women diagnosed with breast cancer are vulnerable to preadjuvant therapy cognitive dysfunction have led to investigations focused on factors that predispose certain women to these burdensome cognitive changes. A number of proposed mechanisms have emerged to account for observed changes and variation in preadjuvant therapy cognitive performance including the biology of the cancer itself [5,6,7,8]. Breast carcinoma biology is heterogeneous and characterized by high degrees of molecular and pathologic diversity both among breast cancers diagnosed in different individuals (i.e., intertumor) and within the same individual (i.e., intratumor). The ability of intertumor pathologic tumor feature (PTF) heterogeneity to account for observed variability in cognitive performance among women diagnosed with breast cancer is a intriguing hypothesis [9,10,11]
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